There’s been a lot of buzz lately about a phenomenon called “the entourage effect,” but what is it?

The idea behind this effect is that when we combine compounds in their natural state we don’t end up with the sum of the parts but rather a multiplying effect. With cannabis, thousands of natural compounds within the plant interact together and with the human body to produce a more meaningful effect than what you’d experience with any single one of the compounds used alone.

This term “entourage effect” was only first introduced around the year 2000, by the Israeli chemist who first who first discovered THC as the main psychoactive component of cannabis. It’s discovery helps explain why different cannabis strains may have different effects depending on the individual. Since strains can differ vastly in their chemical profiles, they can cause an equally vast number of experiences.

Lack of clinical trial research has given rise to critics of the entourage effect who claim that it does not exist, but in fact, it’s very concept is rooted in the centuries-old practice of whole plant medicine. The basic concept is that the chemical compounds found in medicinal plants work together to help that plant to offer its own power to provide healing.

The entourage effect

In the original study, Rafael Mechoulam Mechoulam and fellow chemist Shimon Ben-Shabat examined the interactions between compounds in the cannabis plant and found that certain cannabinoids, which had no effect on their own, could be used to help other cannabinoids in the plant to work more effectively. Other studies since back this initial finding, yet the concept of “the entourage effect” somewhat surprisingly remains a debated topic.

There’s no debate however to Dr. Ethan Russo, who is a Seattle based board certified neurologist and has done immense research on psycho-pharmacology. Former president of the International Cannabinoid Research Society and a former Chairman for the International Association for Cannabinoid Medicines, after 20 years of clinical practice, Dr. Russo took a full-time consulting position with a company out of Britain that develops cannabis based pharmaceuticals.

Dr. Russo is recognized internationally for his research on cannabis compounds and their effects in the body. His research found that “complementary pharmacological activities that may strengthen and broaden clinical applications and improve the therapeutic index of cannabis extracts.” Through these findings he discovered “synergistic effects” between different compounds that enhance and boost each other when combined.

In this we recognize isolated cannabinoids as if each has a list of specific effects. All of Dr. Russo’s research suggests that these effects can be mitigated, or enhanced, when they are paired with other chemical compounds that naturally appear in whole-plant cannabis.

While THC and CBD may be the most famous cannabinoids, they are by no means the only ones. In fact, they’re just two among many important players within the cannabis plant that work together to produce a number of potential therapeutic effects. There are at least 113 known cannabinoids found in cannabis, which bind to receptors in the human body’s endocannabinoid system, specifically the CB1 and CB2 receptors.

If you closely inspect your cannabis flowers, you’ll notice they’re enrobed in a layer of crystal resin that’s sticky to the touch. These crystals house thousands of compounds, including these cannabinoids and a number of terpenes and flavonoids. If you take pure THC, which we know is the main psychoactive ingredient in cannabis, you’ll experience “a high that has no specific character, so that seems boring,” says Mowgli Holmes, a geneticist and founder of a cannabis genetics company Phylos Bioscience. What gives cannabis “character,” in his similar view, are the hundreds of other chemicals it contains.

So what are the hundreds of other chemicals cannabis can contain other than cannabinoids? Dr. Russo examined the benefits of using products containing certain cannabinoids with specific terpenes. Terpenes are essential oils that naturally occur and give cannabis plants distinctive aromas and flavors. His research revealed that terpenes “could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections.”

There is still much research to be done however to determine how all these fascinating chemicals react on a molecular level. In a 2011 review published in the British Journal of Pharmacology, chemists found similar interactions between cannabinoids and terpenes.

It’s believed that when the terpenes remain in a cannabis based product, the benefits are magnified. Researchers discovered that a terpene, linalool, combined with a cannabinoid like CBD, could be used as an effective anti-anxiety medication. Whereas combining linalool with THC makes for a potent sedative, or combining the terpene alpha-pinene with THC helps to retain acetylcholine (a molecule that aids in memory retention) and could help to mitigate the short-term memory loss caused by THC.

The power of scent in the entourage effect seems like a never ending list of fascinating molecular combinations. Limonene is an energizing terpene that can alleviate depression symptoms. Beta- Caryophyllene is powerful in reducing inflammation throughout the body, including the gastrointestinal system. Myrcene has sedative effects which promote calmness and provide relief from anxiety. Linalool is also an anti-anxiety and capable of acting as an anti-microbial. Pinene combats cognitive and memory issues by increasing focus. Multiple terpenes can be used in conjunction to treat a variety of issues in a single dose.

So while whole plant products with terpenes and full spectrum cannabinoids have high efficiency and are more potent than using an isolated compound, we see THC and CBD isolated in clinically approved medications. The reason for this is largely due to the regulatory standards that surround modern medicine. In essence, isolated compounds are much easier to dose, measure and track than a compound found naturally in a plant.

Medicines which are approved in the U.S. by the FDA have to be standardized, meaning that every dose must contain an exact amount of THC, something which can be difficult to guarantee in smokable cannabis, which usually comes with a THC content range rather than an exact measurement. This is the same as what we see prescribed by most doctors in Canada, but thankfully that is changing as legalization pushes the advances of medicinal cannabis.

Isolating constituents from the rest of the components that make up the whole-cannabis plant may offer MDs precision in prescribing, but most anecdotal evidence proves the endocannabinoid system responds more favourably to a full flower cannabis experience.

Consider the drug Marinol, a synthetic form of THC available since the 1980s. It is known to be a good appetite stimulant, but it’s also known to make patients high and paranoid. “When you just stimulate the CB1 receptor with this pure molecule, it's very intoxicating and patients don't tolerate it very well,” says Adie Wilson-Poe, who researches cannabis for pain management at Washington University in St. Louis.

Drugs like Sativex, which combines THC with CBD, or even pure cannabis flower or extracts, and is known to be tolerated by patients much better. “We specifically see that CBD protects against the paranoia and anxiety and the racing heart that THC produces,” Wilson-Poe says.

For smokers, flower vapers, or those making their own edibles by infusing flower into fats, what you will be experience is essentially the entourage effect. In our recent #wcw feature with Katrina Malmqvist of Gräs, she explained how the entourage effect is present in her fat bomb micro dose edibles.

"Since cannabinoids are fat soluble, I began infusing cannabis into organic coconut oil, which I found to be the best carrier. What I discovered was what we call the entourage effect; a microdose with full flower infusion of just 3mg was giving such a beautiful effect. It is long lasting, and delivers this slow, wonderful elevation that I found really helped me deal with some postpartum anxiety I was experiencing."

Unlike the isolated compounds, the full flower infuses into the carrier oils and is delivered to the body to produce a “next-level” high. Find this fascinating? So do we. To educate yourself more on microdosing, terpenes or the endocannabinoid system visit our special interest groups.